Method of using endocardial impedance for assessing tissue heating during ablation

ABSTRACT

A method of locating infarcted myocardial tissue in a beating heart includes the step of inserting an impedance measuring tip of a catheter into the chamber of the beating heart, particularly the left or right ventricle, and measuring the impedance of the endocardium at various locations within the chamber of the beating heart. The values measured are compared to impedance values with a predetermined range of values to identify an infarcted area of myocardium and distinguish such area from normal myocardium. The measurements are also compared to a range of values for an infarction border zone. In accordance with the invention, the infarction border zone may be located. The infarction border zone is a significant source of arrhythmia, and particularly of ventricular tachycardia. Further, in accordance with the methods of the present invention, the risk of arrhythmia in a beating heart may be substantially reduced or eliminated by ablating endocardium within the infarction border zone utilizing the same catheter tip. Impedance measurements may also be utilized to assess the adequacy of the electrode-tissue contact, particularly in a fluid filled body organ or cavity. Further, the effectiveness of the ablation of the tissue may be determined by determining the degree of heating of the tissue by measuring the change in impedance in the area of ablation.

This application is a division of application Ser. No. 08/188,514, filedJan. 28, 1994, which is now pending.

FIELD OF THE INVENTION

The present invention relates to methods of using measurements ofendocardial impedance for the determination of arrhythmiogenic sites forcatheter ablation, assessing catheter-tissue contact and methods ofconfirming tissue ablation during and after energy delivery. Moreparticularly, the present invention relates to methods of determining aninfarction border zone in a beating, post-myocardial infarcted heart,using impedance measurements to insure adequate catheter-tissue contactand measuring the impedance as a confirmation of heating of the tissueduring the ablation process, the later two being useful on varioustissues and organs and not limited to cardiac applications.

BACKGROUND OF THE INVENTION

It has been known for some time that one of the long term sequelae of amyocardial infarction is the generation of arrhythmias, such astachycardia which may result in fibrillation of the heart and suddendeath. Accordingly, for some time, efforts have been directed atreducing the risk of such arrhythmias. For years, attempts have beenmade to reduce the risk of arrhythmia by pharmacological treatment.

More recently, a surgical approach to the eradication of tissue whichgenerates ventricular tachycardia has been utilized which renders thetarget endocardium and sub-endocardium electrically inert or surgicallyremoves it. This surgical procedure has been demonstrated to be highlyeffective, however perioperative mortality is high due to leftventricular failure, and only a small percentage of patients withventricular tachycardia are candidates for this procedure.

Most recently, attempts to eradicate arrhythmic tissue have included theapplication of radiofrequency energy via an electrode mounted on acatheter tip, known as "catheter ablation". For example, see U.S. Pat.No. 5,239,999--Imran.

There are significant problems with the catheter ablation process aspreviously practiced, including the inability to judge adequate contactbetween the ablating electrode and the target endocardium. Anotherproblem is the inability to locate appropriate targets for ablation.Still another problem is the inability to determine when theradiofrequency energy applied via an electrode mounted on a cathetersuccessfully ablates the tissue intended to be ablated.

In the past, techniques to localize the endocardial origin ofventricular tachycardia in the setting of chronic myocardial infarctionhave utilized only electrogram characteristics. These techniques haveincluded sinus rhythm mapping, activation mapping, pace-mapping andentrainment mapping. These techniques have poor specificity forlocalization of the site of origin of ventricular tachycardia. Inaddition, to properly perform some of these techniques, long periods ofsustained tachycardia are necessary, often placing a significanthemodynamic burden on the patient.

SUMMARY OF THE INVENTION

The present invention is directed to a method of locating infarctedmyocardial tissue in a beating heart which includes the step ofinserting an impedance measuring tip of a catheter into a chamber of abeating heart, measuring the impedance of the endocardium at variouslocations within the chamber of the beating heart and comparing themeasured impedance values with a predetermined range of values and/orassessing differences in impedance ranges to identify an infarcted areaof myocardium and distinguish such area from normal myocardium.

It has been found that there is a two fold crease in impedance measuredon the endocardium of infarcted tissue as contrasted to normalendocardium. Ranges of values may be tabulated and impedancemeasurements compared with these values. Alternatively, measurements maybe taken on various surfaces of the endocardium and compared with eachother to determine infarcted areas as well as border zones betweeninfarcted endocardium and normal endocardium. The border zone betweennormal and infarcted endocardium, particularly in the ventricles, isoften a source of the generation of an arrhythmia such as ventriculartachycardia.

In accordance with the present invention, a method of reducing the riskof arrhythmia in a beating heart utilizes the step of inserting a tip ofa catheter into a chamber of a beating heart wherein the tip is adaptedfor both impedance measurement and ablation. The impedance of theendocardium at various locations within the chamber of the beating heartis measured using the tip of the catheter in the measuring mode ofoperation. Once the border zone between normal and infarctedendocardium, referred to herein as the infarction border zone islocated, sufficient energy is applied to the tip of the catheter toablate endocardium in the infarction border zone.

Further in accordance with the present invention, a method is providedof assessing the adequacy of electrode-tissue contact in a fluid filledorgan which includes the steps of inserting an impedance measuringelectrode mounted on a catheter into a desired portion of a fluid filledorgan and determining whether the electrode is in contact with the organtissue based on the impedance value. In a presently preferredembodiment, the method is utilized to assess the adequacy of electrodecontact with the endocardium in a catheter ablation process by firstmeasuring the impedance value when the electrode is in blood, such as inthe aorta outside of the heart to determine a base line value anddetecting the change in impedance when the electrode comes in contactwith the endocardium.

Further, in accordance with the present invention, a method of assessingthe effectiveness of tissue ablation utilizes the steps of measuring theimpedance of tissue at or around the area of tissue to be ablated atbody temperature and measuring the impedance of the tissue in the areabeing ablated during the application of ablation energy inorder toassess the degree of heating of the tissue. It has been found thattissue impedance declines substantially proportionally to tissuetemperature during the ablation process. Accordingly, in cardiaccatheter ablation, the effectiveness of the ablation of the endocardiummay be monitored to insure, by measuring the change in impedance, thatsufficient heating of the endocardium has taken place to insure tissueablation adequate to eliminate the arrhythmiogenic site.

The terms impedance or electrical impedance as utilized herein areintended in their broadest sense, that is including the resistivecomponent and/or inductive reactance and/or capacitive reactance,including the condition wherein the capacitive and inductive reactancesmay cancel or are non-existent leaving only the resistive component asthe impedance. In a co-pending application filed the same day as thisapplication, application Ser. No. 08/138,142, filed by some of the sameapplicants herein and entitled Systems and Methods for Examining theElectrical Characteristics of Cardiac Tissue, the term"E-Characteristic" has been utilized in connection with such impedanceand resistance values.

BRIEF DESCRIPTION OF THE DRAWINGS

For the purpose of illustrating the invention, there are shown in thedrawings forms which are presently preferred; it being understood,however, that this invention is not limited to the precise arrangementsand instrumentalities shown.

FIG. 1 is a view in perspective of a catheter tip which may be utilizedin practicing the method of the present invention.

FIG. 2 is a graph of impedance values illustrative of the principles ofthe method of the present invention.

FIG. 3 is an elevation view of an alternate embodiment of a catheter tipwhich may be utilized in practicing the method of the present invention.

FIG. 4 is a graph of decreasing impedance values with increasingtemperature of tissue being ablated in accordance with the method of thepresent invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

A myocardial infraction incurs when an area of the heart is deprived ofblood and therefore oxygen. After the death of cardiac tissue, thetissue is replaced with scar tissue. At the border between the scartissue and the normal endocardium, there is a mixture of normal cellsand scar tissue. Normal endocardium is comprised mainly of cardiacmuscle cells. Infarcted myocardium is comprised mainly of proteinstrands without cells. The infarction border zone represents a gradualtransition in tissue protein strand content. It is the protein strandcontent which causes the differences in impedance between normal,infarction and infarction border zone. Infarction border zone is an areaof endocardium which often generates arrhythmias such as ventriculartachycardia.

It is the infarction border zone which is desired to be located for thepurposes of ablation.

In accordance with the method of the present invention, it has beenfound that areas of normal tissue, infarcted tissue and areasimmediately adjacent infarcted tissue, referred to herein as theinfarction border zone may be identified or located within a beatingheart by measuring the impedance of the endocardium at various points.It has been found in accordance with the method of the present inventionthat the three types of myocardial tissue namely normal, infarcted andinfarction border zone tissue, present distinct ranges of impedance whenmeasured in accordance with the methods of the present invention. It hasbeen found that there is substantially a two fold increase in theimpedance values of normal tissue as contrasted to infarcted tissue.Further, there is approximately a one fold increase in the infarctionborder zone as compared to infarcted tissue.

Although not limited to the locating of arrhythmias arising in theventricles, the present invention is particularly useful for locatingthe source of such ventricular tachycardias. Further, in accordance withthe present invention, once such potential source of arrhythmia, namelythe infarction border zone, has been located, it may be ablated inaccordance with the methods of the present invention utilizing the samecatheter tip by the application of suitable amounts of RF energy,thereby reducing or eliminating the risk of arrhythmias such asventricular tachycardias.

In accordance with the present invention, a catheter tip such as thatshown in FIG. 1 may be utilized, although various other types ofcatheter tips may be utilized in practicing the method of the presentinvention. In accordance with the method of the present invention, ithas been found to be advantageous to have a catheter tip design whichcomes directly into contact with the endocardium in such a manner as toreduce contact of the measuring tip with the blood in the beating heart,thereby enabling direct measurement of the impedance of the endocardium,as contrasted to the impedance of blood which is of a significantlylower value. An important concept in the technique of utilizingelectrodes for assessing the adequacy of tissue contact is that theelectrode be configured in such a way as to permit contact solely withthe tissue of interest. The impedance value obtained by the electrodewill then reflect the impedance of the contacted tissue only. Partialcontact with tissue will render an ambiguous impedance value. It isfurther preferred that the catheter tip have heat dissipating designfeatures for more accurate readings.

One suitable electrode for a catheter tip is illustrated in FIG. 1wherein the tip is provided with a disc shape 10 which is provided witha predetermined significant depth which enhances heat dissipation. Inthe one example illustrated in FIG. 1, the disc shaped catheter maypreferably have dimensions of a diameter 12 of 2.33 mm and a depth of0.25 mm. However, it is understood that other dimensions of cathetertips may be utilized in practicing the method of the present invention.The catheter shaft 14 is preferably fitted with a recording electrode 16which acts as a second electrode for recording purposes, such asrecording local electrograms. The catheter utilized herein may beprovided with one or more other electrodes so that various electrogramsmay be measured. Electrograms may also be measured with the impedancemeasurement electrode. Adequate recording of electrograms does notrequire sole contact of an electrode with the endocardial area ofinterest.

Referring to FIG. 3, there is shown another embodiment of an electrode30 mounted on a catheter tip 32 which may be utilized in practicing thepresent invention. Catheter tip shown in FIG. 3 is provided with a sharptip 34 and is relatively long, being 2 millimeters long and of arelatively small diameter, approximately 0.2 millimeters. The electrode30 may be utilized to achieve exclusive tissue contact at odd angles. Itwill be apparent to those skilled in the art that various dimensions andmodifications may be made to the electrodes for the catheter tips inaccordance with the present invention.

As will be described more fully hereinafter, contact of such anelectrode with the endocardium will provide a much higher impedancevalue than contact with the surrounding blood, thereby providing a meansof endocardial contact assessment. The impedance difference between theendocardium and the blood depends on the surface area of the electrode,smaller surface areas record larger differences.

In practicing the method of the present invention, the catheter tip isused for both measuring impedance and ablating tissue. Tissue is ablatedby the application of RF energy in suitable amounts, as is well known inthe electrode catheterization art. The catheter may be guided to anychamber or area of the heart. In practicing the method of the presentinvention, the measuring electrode may be mounted in any way that allowsdirect contact with the endocardium. For example, left ventricularendocardial mapping may be performed by percutaneous insertion of thecatheter into the femoral artery using the Seldinger technique, thenretrograde passage of the catheter via the aorta and into the ventricleafter crossing the aortic valve. Of course, access to any endocardialsite in either atria or either ventricle may be achieved. In addition,mapping of the epicardium may be performed by thoracotomy and directapplication of the electrode to the heart. The guidance of cathetersinto the heart, often using fluoroscopy, is known as cardiaccatheterization, and is well known to those skilled in the art and neednot be described here in detail.

Once the catheter tip is located in the appropriate chamber of theheart, the catheter tip may be manipulated to engage the myocardial areaof interest with an appropriate contact pressure to achieve sole tissuecontact to allow accurate measurement of the impedance at variouslocations. Utilization of the rendered impedance value may be performedusing normal values based on research on subjects with normal hearts,and/or by using the impedance values measured in clearly normal areas ofthe heart of the subject undergoing investigation. By comparing valuesin these ways, areas of infarction or infarction bordering endocardiummay be discerned. In this manner, suitable sites for application ofenergy for the performance of catheter ablation may be determined.Adequacy of electrode-tissue contact may be assessed as describedhereinafter.

Ranges of impedance may be predetermined for normal endocardium, denselyinfarcted endocardium and infarction border zone endocardium asillustrated in FIG. 2. FIG. 2 illustrates specific values for normal,infarcted and infarction border zone endocardium measured in asignificant number of sheep measured at 550 kHz. As illustrated in FIG.2 at 20, normal endocardium tissue has an impedance range as illustratedwith a mean in the neighborhood of 350 ohms. Endocardium in theinfarction border zone has an impedance range as illustrated at 22 witha mean value of about 250 ohms. Densely infarcted endocardium has atissue range as illustrated at 24 with a mean value of about 100 ohms.Generally, impedance values measured on infarcted endocardium wereapproximately 25% of those in normal endocardium and impedance valuesfrom infarction border areas were approximately 60-70% of those innormal endocardium. Although specific values may vary by electrode tipand the like, easily discernable differences in impedance arereproducibly achieved between normal, infarction border zone andinfarcted endocardium.

In this manner, by comparing values measured at various points withinthe endocardium, infarcted tissue may be determined. Furthermore, normaltissue may be determined and most importantly, the infarction borderzone may be determined. The infarction border zone has been determinedto be a frequent source of arrhythmias, particularly of ventriculartachycardia. Accordingly, by use of the method of the present invention,sites for ablation within a beating heart may be determined utilizingcardiac catheterization techniques, and such sources of potentialarrhythmias may be ablated, thereby reducing or eliminating the risk ofarrhythmia, and particularly of ventricular tachycardia.

The method of determining the tissue to be ablated described herein isnot limited to cardiac catheterization ablation for purposes ofeliminating arrhythmiogenic sites. The method of the present inventionmay be utilized to measure impedances within various organs or bodycavities to detect differences in tissue impedance to enable adetermination as to a site to be ablated. For example, a tumor in theliver or bladder may be located by the detection of different impedancevalues between normal and tumor tissue, thereby enabling the ablation ofsuch tumor tissue. The method of the present invention may be utilizedto detect various different conditions in tissue which are accompaniedby a change in impedance values.

In accordance with the method of the present invention, assessment ofadequate contact between the electrode on the catheter tip and tissue ina fluid filled cavity or organ may be assessed. In a preferredapplication of practicing the method of the present invention, adequacyof electrode-endocardium contact may be assessed in a blood filledpumping heart. It has been found that there is significant impedancedifference between the impedance of blood and endocardium tissue. Thisdifference is very pronounced between blood and normal endocardiumtissue. However, even with respect to infarcted endocardium, theimpedance of the blood is characteristically measured at rangesapproximately 25% less than the values achieved for infarcted tissue.This 25% change in impedance may be used to make the determination oralternatively specific values may be obtained for each patient by makingan impedance measurement in the blood, preferably in a vessel, such asthe aorta, outside of the heart, and another impedance measurement whenthe electrode is in direct stable placement with the endocardium asdetermined visually using fluoroscopy. Accordingly, by noting ormonitoring the values of measured impedance, an assessment may be madeas to whether there is adequate contact between the catheter tipelectrode and the endocardium.

When radiofrequency energy is passed through an electrode which is incontact with the inside of the heart (endocardium), the volume of theendocardium which is in contact with the electrode will heat. If thetissue gets hot enough, it will die. If the tissue which is killed waspart of an aberrant electrical circuit, such as those which causecardiac arrhythmias, the arrhythmia will be cured. If the contactbetween the electrode and the endocardium is poor, the radiofrequencyenergy is quickly dissipated in the blood passing through the heart, andno significant accumulation of heat is achieved in the endocardium.Accordingly, the foregoing method of assessing adequate contact betweenthe electrode and the endocardium is of great importance.

This method of assessing the adequacy of electrode-tissue contact may beutilized in any body cavity or organ which has a direct blood or otherfluid (e.g. cerebrospinal fluid) interface.

Further, even if the contact is adequate, it is important to determinethat the RF energy applied via the electrode mounted on the catheter tipis causing sufficient heating of the endocardium to allow for successfulablation. Should the endocardium be heated only to a lower temperatureat which it can survive and return to normal function, if this tissuewere a critical part of the propagation path of an arrhythmia, it ispossible that the arrhythmia which was thought to be permanentlyeradicated during a given catheter ablation procedure may be onlytemporarily damaged. Unexpected recurrence of arrhythmias may lead todangerous symptoms, including death in some cases and to morbidity,expense and risk of repeated hospitalization and further procedures.Accordingly, it is important to be able to determine during andimmediately after the ablation process that the target endocardium to beablated was sufficiently heated so as to sufficiently ablate theparticular area of endocardium to prevent further arrhythmia generation.

In accordance with the present invention, it has been found that actualheating of the myocardium during the application of RF energy isassociated with a reproducible linear change in the impedance of themyocardium. See FIG. 4. Since heating by the application of RF energycauses the ablation, it is important that the degree of heating of theendocardium or other tissue to be ablated be determined. Sufficientheating of the endocardium is capable of curing an arrhythmia resultingfrom that tissue. A temperature of approximately 50 degrees centigradeis required to successfully ablate myocardium. It is possible forendocardium which is heated to lower temperatures to survive and returnto normal function.

In order to assess or monitor the heating of the endocardium, theimpedance of the endocardium may be monitored during the application ofthe RF energy and/or immediately after the application of the RF energy.These impedance measurements are compared to a base line impedance valueestablished by measuring the impedance in or around the area to beablated at normal body temperature, preferably, but not necessarily,immediately before the application of the RF energy for ablation. Once aconsistent measurement of impedance is obtained in the base line state,radiofrequency energy or other ablation energy is applied. As themyocardium located at the surface of the electrode heats, localimpedance changes, and such changes may be continuously measured via theenergy delivering electrode.

In practicing the method of assessing the degree of heating during theablation process, as well as in the electrode-tissue contact assessment,it is preferable to use a catheter electrode such as that shown in FIG.1 although other types of electrodes may be utilized in practicing themethod the present invention so long as the design criteria outlinedabove are taken into account.

FIG. 4 is illustrative of the relationship between increasing tissuetemperature and decreasing impedance. FIG. 4 illustrates data obtainedusing the electrode of FIG. 1 on the epicardium of live pigs, measuredin unipolar fashion at 550 kilohertz. A substantially linear decrease inimpedance was shown in association with rising tissue temperature at theelectrode surface induced by the application of RF energy. This patternwas highly reproducible. Accordingly, the tissue impedance monitoringprovides reliable information of tissue temperature at the site ofenergy application via the electrode. It is believed that this is theonly unequivocal evidence of actual tissue heating.

Although the data is reproducible and values may be established in whichabsolute impedance measurement correlate with a predetermined amount oftissue heating, in the preferred method of practicing the invention,each patient's impedance values at body temperature, before applicationof energy may be used to establish the base line. In this way, eachpatient acts as his/her own standard of reference, from which the degreeof tissue heating may be judged from the amount of tissue impedancedecrease with each energy application.

Numerous variations may be made in practicing the methods of the presentinvention without departing from the spirit or scope of the presentinvention. Various frequencies may be utilized in the measuring processranging from 1 kilohertz to 1 megahertz. It has been found that by usingfrequencies at less than 100 kilohertz, better resolution of impedancevalues is obtained for demonstrating tissue heating. In the preferredmethod of practicing the invention, impedance has been measured atfrequencies at which RF energy is applied through commercially availabledevices, namely in the 500 to 750 kilohertz range. Although largerdifferences in ranges of impedance values between normal, infarctionborder and infarcted tissues are found at lower frequencies, frequenciesutilized may be up into the megahertz range. However, preferably thefrequency used is less than 1,000 kHz. In a preferred method ofpracticing the invention to date, impedance measurements have been madeat 550 kHz. At lower frequency ranges, particularly in the 1 kHz range,although the largest differences between ranges of impedance values fornormal, infarcted and infarction border zone tissue are observed,electrode polarization artifacts may present a serious problem. However,as referred to above, various other types of catheter tips may beutilized, including a catheter tip having four spaced electrodes mountedin an insulative base. A fixed current may be passed through endocardiumbetween the two outer electrodes and the voltage developed in theendocardium between the two inner electrodes may be measured. Theimpedance may be readily calculated by the equipment as the ratio ofvoltage to current. Typically, a small subthreshold current ofapproximately 15 micro-amperes alternating current may be utilized forthis purpose.

It is further noted that the methods described and illustrated hereinare not limited to use in the myocardium. The impedance measuring methodto determine differences in tissue, the method of determining whetherthe electrode is in contact with the tissue and the method of assessingadequate ablation of undesired tissue may be used in variousapplications in the body, including, but not limited to, ablation oftumors, cancerous or benign, or the like.

In view of the above, the present invention may be embodied in otherspecific forms without departing from the spirit or essential attributesthereof and, accordingly, reference should be made to the appendedclaims, rather than to the foregoing specification as indicating thescope of the invention.

We claim:
 1. A method for assessing effectiveness of tissue ablution,comprising the steps of:measuring impedance of tissue at an ablationarea at normal body temperature to establish a baseline impedance value;monitoring impedance of the tissue in an area being ablated immediatelyafter application of ablation energy; comparing the base line impedancevalue to the monitored tissue impedance to determine an absoluteimpedance measurement; and correlating an amount of tissue heating tothe absolute impedance measurement, a substantially linear decrease inimpedance corresponding to rising tissue temperature and effectivetissue ablation.
 2. A method in accordance with claim 1, wherein thepreviously recited impedance measuring steps are carried out utilizingan electrode mounted on a tip of a catheter.
 3. A method in accordancewith claim 2, wherein said method is utilized within a beating heart todetermine adequacy of endocardial tissue ablation in a beating heart. 4.A method for assessing effectiveness of tissue ablation, comprising thestepsinserting into a beating heart a catheter having an electrode witha design which comes directly into contact with endocardium in such amanner as to minimize contact of a measuring electrode with blood in thebeating heart; measuring impedance of endocardium at an ablation area atnormal body temperature to establish a baseline impedance value:monitoring impedance of the endocardium in an area being ablatedimmediately after application of ablation energy; comparing the baselineimpedance value to the monitored endocardium impedance to determine anabsolute impedance measurement; and correlating an amount of endocardiumheating to the absolute impedance measurement, a substantially lineardecrease in impedance corresponding to rising tissue temperature andeffective tissue ablation.
 5. A method for assessing effectiveness oftissue ablation in accordance with claim 4 wherein said catheterelectrode is placed in it entirety directly in contact with theendocardium during said impedance measuring steps.
 6. A method forassessing effectiveness of tissue ablation in accordance with claim 4wherein said steps of measuring impedance are performed using a sharptipped catheter electrode to achieve exclusive tissue contact bypiercing endocardium.